HCAR1 (also known as GPR81) is a G-protein-coupled receptor that serves as the primary cellular receptor for lactate, mediating diverse physiological and pathological processes through Gi-protein signaling pathways 12. The receptor plays a crucial role in metabolic regulation, where lactate binding activates anti-lipolytic effects and influences energy metabolism 1. In cancer biology, HCAR1 contributes to tumor progression through multiple mechanisms: it drives cachexia by activating a Gi-Gβγ-RhoA/ROCK1-p38 signaling cascade in adipose tissue 1, promotes immunosuppression by inducing CCL2/CCL7 chemokine expression that recruits immunosuppressive myeloid-derived suppressor cells 3, and regulates ferroptosis resistance through AMPK-SCD1 pathway modulation 4. HCAR1 also mediates beneficial effects in tissue homeostasis, promoting intestinal stem cell proliferation and epithelial development through Wnt/β-catenin signaling 2. However, chr12 activation can be detrimental, as demonstrated in osteoarthritis where HCAR1 signaling promotes chondrocyte damage via PI3K/Akt-mediated NOX4 upregulation and oxidative stress 5. The receptor's involvement in exercise-induced angiogenesis suggests additional roles in vascular health 6. These findings highlight HCAR1 as a promising therapeutic target for cancer cachexia, immunotherapy resistance, and metabolic disorders.